Epigenetics, Stress, and Their Potential Impact on Brain Network Function: A Focus on the Schizophrenia Diatheses

Abstract

The recent sociodevelopmental cognitive model of schizophrenia/psychosis is a highly influential and compelling compendium of research findings. Here, we present logical extensions to this model incorporating ideas drawn from epigenetic mediation of psychiatric disease, and the plausible effects of epigenetics on the emergence of brain network function and dysfunction in adolescence. We discuss how gene–environment interactions, effected by epigenetic mechanisms, might in particular mediate the stress response (itself heavily implicated in the emergence of schizophrenia). Next, we discuss the plausible relevance of this framework for adolescent genetic risk populations, a risk group characterized by vexing and difficult-to-explain heterogeneity. We then discuss how exploring relationships between epigenetics and brain network dysfunction (a strongly validated finding in risk populations) can enhance understanding of the relationship between stress, epigenetics, and functional neurobiology, and the relevance of this relationship for the eventual emergence of schizophrenia/psychosis. We suggest that these considerations can expand the impact of models such as the sociodevelopmental cognitive model, increasing their explanatory reach. Ultimately, integration of these lines of research may enhance efforts of early identification, intervention, and treatment in adolescents at-risk for schizophrenia.

Stress-Induced Reduction of Dorsal Striatal D2 Dopamine Receptors Prevents Retention of a Newly Acquired Adaptive Coping Strategy

“…Development or expression of immobility in FSt is disrupted by proximal stress experiences ( Molina et al, 1994 ; Alcaro et al, 2002 ; Becker et al, 2008 ; Mozhui et al, 2010 ), an observation that further support the translational value of this animal model because proximal adverse experiences contribute to development of mental diseases ( Dias-Ferreira et al, 2009 ; Daskalakis et al, 2013 ; Gourley et al, 2013 ; Diwadkar et al, 2014 ; Reul, 2014 ; Eagle et al, 2015 ). The neurobiological mechanisms mediating the disruptive effects of proximal stress experiences on subsequent coping with FSt are still poorly understood, although disturbances of learning processes could play a major role ( Mitchell and Meaney, 1991 ; Colelli et al, 2014 ; Reul, 2014 ).…”

Perspectives on stress resilience and adolescent neurobehavioral function

“…4 ). For instance, stress-induced epigenetic changes, either during perinatal and/or adolescent stages of development ( McGowan and Szyf, 2010 , Chakraverty et al., 2014 , Lo and Zhou, 2014 , Diwadkar et al., 2014 ), will need to be examined and whether these alterations in the individual's epigenetic landscape are context- or germline-dependent ( Crews, 2008 ). Furthermore, future experiments will need to investigate sex differences in these potential mechanisms mediating stress resilience, given the significant role of sex in modulating responsiveness to stressors ( Becker et al., 2007 , Bangasser and Valentino, 2014 ).…”

MRI volumetric changes in hippocampal subfields in psychosis: a protocol for a systematic review and meta-analysis

“…Studies have found that early life stress may result in microstructural hippocampal changes such as reduced neurogenesis and dendritogenesis [ 48 ], leading to reduced hippocampal volumes [ 20 ]. Early life adversity is thought to interact with inherent genetic vulnerabilities resulting in hippocampal morphological changes and dysfunctional information processing [ 14 ]. The hippocampus is the major hub integrating memory and emotion and dispersing information throughout the limbic system to and from the amygdala, thalamic, cingulate, and frontal regions [ 44 , 47 , 57 ].…”